Long-Term Risk of Cardiovascular Disease Among Type 2 Diabetes Patients According to Average and Visit-to-Visit Variations of HbA1c Levels During the First 3 Years of Diabetes Diagnosis

Background: It remains unclear whether a combination of glycemic variability and glycated hemoglobin (HbA1c) status leads to a higher incidence of cardiovascular disease (CVD). Therefore, to investigate CVD risk according to the glucose control status during early diabetes, we examined visit-to-visit HbA1c variability among patients with type 2 diabetes (T2DM). Methods: In this 9-year retrospective study, we measured HbA1c levels at each visit and tracked the change in HbA1c levels for 3 years after the first presentation (observation window) in newly diagnosed T2DM patients. We later assessed the occurrence of CVD in the last 3 years (target outcome window) of the study period after allowing a 3-year buffering window. The HbA1c variability score (HVS; divided into quartiles, HVSQ1-4) was used to determine visit-to-visit HbA1c variability. Results: Among 4, 817 enrolled T2DM patients, the mean HbA1c level was < 7% for the first 3 years. The group with the lowest HVS had the lowest rate of CVD (9. 4%; 104/1, 109 patients). The highest incidence of CVD of 26. 7% (8/30 patients) was found in HVS 9. 0%Q3, which was significantly higher than that in HVS 6. 0-6. 9%Q1 (P = 0. 006), HVS 6. 0-6. 9%Q2 (P = 0. 013), HVS 6. 0-6. 9%Q3 (P = 0. 018), and HVS 7. 0-7. 9%Q3 (P = 0. 040). Conclusion: To our knowledge, this is the first long-term study to analyze the importance of both HbA1c change and visit-to-visit HbA1c variability during outpatient visits within the first 3 years. Lowering glucose levels during early diabetes may be more critical than reducing visit-to-visit HbA1c variability.